Psychedelic Research Recap June 2024
Psychedelic Research Recap June 2024
Welcome back to our monthly update on psychedelic research! I’m sorry this one’s a bit late – I got married last month, so things have been busy. But I’m excited to share what’s new in this fast-changing field.
This month, we’ve got a mix of different studies to look at. We’ll see research on combining psychedelics or tweaking their chemical structure, new findings on ayahuasca, some big-picture reviews, and studies focused on single psychedelic compounds. Topics range from seizure risk and memory effects to brain connectivity changes and new treatments for depression.
We’ll also explore how psychedelic experiences can change people’s lives, whether microdosing is just a placebo effect, and the role of purging in ayahuasca healing. Other exciting areas include combining psychedelics with mindfulness, how these substances create visual effects in the brain, their impact on sleep, and new ethics guidelines for using psychedelics in healthcare. There’s a lot to dig into, so let’s get started!
This month’s recap is made possible by our supporting members.
Check out the research link overview for all the studies we didn’t add to the database.
Comparing, Combining, and Customising Psychedelics
Psychedelic research continues to push boundaries, with recent studies comparing different substances, exploring their effects on memory and brain connectivity, and developing new compounds. In this section, we’ll look at all these ‘combination’ studies.
A study compared the effects of psilocybin and 2C-B on emotional memory encoding. Both substances were found to affect memory similarly despite their different chemical structures. They impaired recollection and familiarity estimates, increased false alarms for emotional stimuli, and influenced metamemory (our understanding of our own memory). These findings suggest that different psychedelics might share common mechanisms in how they affect our memory processes. Previous research published on this study showed other similarities between the two psychedelics and noted that 2C-B could be considered a ‘lighter’ experience.
Another study used fMRI to examine how psilocybin and Salvinorin-A affect brain connectivity in non-human primates. Both substances influenced connectivity around the thalamus, claustrum, prefrontal cortex, and default mode network. However, there were also some differences between the two drugs. This research highlights the importance of the cortico-claustro-cortical network in understanding how psychedelics work in the brain.
A clinical trial tested a new form of ketamine for treating depression. This extended-release ketamine tablet (R-107) showed promising results in people with hard-to-treat depression. The highest dose (180mg) significantly improved depression symptoms compared to a placebo after 13 weeks (though this analysis was done in a small subset (n=29) of participants). Importantly, the treatment was well-tolerated, with minimal side effects like headache and dizziness.
Researchers also examined how memory might play a role in psilocybin’s therapeutic effects. They gave psilocybin along with midazolam, a (benzodiazepine) drug that impairs memory formation. They found that memory impairment was linked to less intense experiences of insight and well-being from psilocybin. This suggests that remembering the psychedelic experience might be important for its benefits.
A pilot study combined esketamine (a form of ketamine) with mindfulness training for people with alcohol problems (AUD). Esketamine seemed to help people engage more with the mindfulness practice and temporarily reduced alcohol cravings. It also led to stronger mystical and dissociative experiences compared to a placebo.
Lastly, researchers are working on developing new psychedelic-inspired compounds. A study looked at three new versions of MDMA, designed to be safer alternatives. These new compounds showed similar effects on serotonin, dopamine, and norepinephrine transporters as MDMA, but had less impact on certain serotonin receptors and were processed differently by the liver. This suggests they might have fewer side effects than MDMA while still providing therapeutic benefits.
Reviews on Safety, Efficacy, and Ethics
Recent reviews in psychedelic research have covered a range of essential topics, from safety concerns to therapeutic potential and ethical considerations. Here, we cover four that stood out (see all reviews from June/this year in our link overview).
A review examined the relationship between classic psychedelics and seizures. The study found that psychedelics may not increase seizure risk in healthy individuals or animals when used alone. However, combining psychedelics with other substances like kambo or lithium could potentially raise the risk. The authors caution that these conclusions are based on limited data and should be interpreted carefully.
Another reviewtackled the ongoing debate about microdosing, specifically whether its effects are mainly due to placebo. The authors analyzed dose-controlled studies of low-dose LSD and psilocybin, identifying eight potential issues that complicate the placebo explanation. These include small sample sizes, limited controlled studies, and possible selection bias. The review concludes that it’s currently unclear whether microdosing is just a placebo effect.
A comprehensive review explored the role of music in psychedelic-assisted therapy (PAT) and Indigenous entheogenic ceremonies. By examining neuroscientific, psychological, and anthropological research, the study highlighted the importance of personalized music protocols in PAT. It also suggests that integrating traditional practices from Indigenous ceremonies into modern treatment models could enhance clinical outcomes.
Lastly, a consensus statement from 27 experts identified critical ethics and policy issues for integrating psychedelic therapies into clinical practice. The statement outlines 20 points of consensus across five ethical areas, including reparations and reciprocity, informed consent, and professional boundaries. It also assigns responsibilities to relevant actors for implementing these recommendations.
Ayahuasca Studies on Purging, Healing, and Alcohol Use
Before we dive into the final group of psychedelic studies, here is a closer look at two ayahuasca studies that were published last month.
A qualitative study at the Takiwasi Centre in Peru explored practitioner perspectives on purging during ayahuasca rituals. The researchers interviewed 11 participants, including healers, plant preparers, and psychotherapists. The study identified three main explanatory models for purging: spiritual-oriented, Amazonian-oriented, and clinical-oriented. All these models emphasized the important connection between purging and healing in ayahuasca-assisted treatment for substance dependence.
Another study looked at the effects of a single dose of ayahuasca on college students with harmful alcohol use. This single-blind feasibility study involved 11 participants who received one dose of ayahuasca (70ml/70kg) along with psychological support. The researchers found a trend towards reduced alcohol consumption after the ayahuasca session, though this effect was not statistically significant after applying corrections. The ayahuasca was well-tolerated, with no serious side effects reported.
Despite these promising findings, ayahuasca remains understudied in scientific research. One major challenge is the variability in ayahuasca brews, which can differ in composition and potency depending on the plants used, preparation methods, and cultural practices. This lack of standardization makes comparing results across studies or drawing definitive conclusions difficult.
Diverse Psychedelic Studies Investigating Transformative Experiences, Visual Imagery, and Sleep Effects
Finally, let’s look at three human studies with ‘just’ one psychedelic, but with novel perspectives.
A studyexamining the transformative nature of psychedelic experiences interviewed 26 participants from psychedelic retreats. The results showed that psychedelics can lead to significant changes in identity, values, beliefs, and behavior. Most participants reported unique insights, and many experienced behavioral changes. The study also found that participants felt well-informed and capable when deciding to use psychedelics, with many reporting an improved ability to make changes in their lives afterward.
Another study reanalyzed data from a randomized controlled trial involving psilocybin. The researchers found that self-inhibition of visual areas in the brain leads to complex imagery experienced by participants. This aligns with existing models of how psychedelics affect brain function, highlighting how bottom-up processes are amplified under their influence.
A third study looked at how ketamine affects sleep in people with treatment-resistant depression (TRD). This secondary analysis of a randomized, double-blind, crossover trial found that ketamine impacts delta and alpha power during sleep. However, it didn’t significantly change overall sleep patterns or mediate its antidepressant and anti-suicidal effects through sleep variables.
Papers Published in June 2024
18 studies from the Blossom database published this month.
Do classic psychedelics increase the risk of seizures? A scoping review
This scoping review (s=27) assesses the relationship between classic psychedelics and seizures. It finds that psychedelics may not increase seizure risk in healthy individuals or animals without other drugs, but concomitant use of substances like kambo or lithium could heighten the risk.
Acute Effects of Hallucinogens on Functional Connectivity: Psilocybin and Salvinorin-A
This fMRI study explores the effects of psilocybin (a serotonergic psychedelic) and Salvinorin-A (a kappa-opioid receptor agonist) on resting-state functional connectivity (FC) in nonhuman primates. It reveals both drugs influence FC around the thalamus, claustrum, prefrontal cortex (PFC), and default mode network (DMN), with similarities and differences noted between them.
Randomized Placebo-Controlled Phase 2 Study of Extended-Release Ketamine Tablets (R-107) for Treatment-Resistant Depression - the BEDROC Study
In this phase 2 randomised, placebo‑controlled enrichment study, extended‑release oral ketamine tablets (R‑107) given twice weekly maintained antidepressant response in treatment‑resistant depression, with the 180 mg dose producing a significant 13‑week MADRS improvement versus placebo (least‑square mean difference −6.1, P = 0.019). R‑107 was generally well tolerated with minimal blood‑pressure, sedation or dissociation effects, showed a dose–response reduction in relapse rates, and most dosing was performed at home.
AlphaFold2 structures guide prospective ligand discovery
Prospective docking of large libraries against unrefined AlphaFold2 (AF2) models of the σ2 and 5‑HT2A receptors yielded hit rates and affinities similar to those from experimental structures, and cryo‑EM of a potent 5‑HT2A ligand showed residue accommodations resembling the AF2 prediction. This demonstrates that AF2 models can sample alternative low‑energy conformations relevant for ligand discovery, extending the utility of structure‑based drug design.
A Transformative Trip? Experiences of Psychedelic Use
Analysing interviews with 26 retreat participants, the study finds that psychedelic experiences can constitute transformative experiences: 20 participants reported insights seemingly inaccessible without psychedelics and 25 of 26 reported changes in identity, values, desires or behaviour (behavioural change was most common). The authors argue this raises neuroethical concerns about consent and moral psychopharmacology and call for person-centred research and ethical inquiry.
Bioisosteric analogs of MDMA: Improving the pharmacological profile?
This in vitro and in silico study investigates whether three new methylenedioxy bioisosteres of MDMA improve its off-target profile. Compared with MDMA, these bioisosteres (ODMA, TDMA, and SeDMA) show similar activity at human serotonin, dopamine, and norepinephrine transporters but decreased agonist activity at 5-HT2A/2B/2C receptors and different hepatic metabolism, suggesting potential as safer therapeutic alternatives.
Is microdosing a placebo? A rapid review of low-dose LSD and psilocybin research
This review (2024) critically assesses the available evidence from dose-controlled studies investigating low doses of LSD and psilocybin. It proposes eight potential issues, such as small sample sizes, a limited number of controlled studies, and the possibility of selection bias, that challenge the claims that microdosing is predominantly a placebo effect. It suggests that it is currently inconclusive whether microdosing is merely a placebo.
Purging to cleanse: a qualitative study of Ayahuasca healing at a drug treatment centre in Peru
This qualitative study (n=11) explores practitioner perspectives on purging during Ayahuasca rituals at the Takiwasi Centre in Peru. Interviews with curanderos, plant preparers, and psychotherapists reveal three main explanatory models: spiritual-oriented, Amazonian-oriented, and clinical-oriented, all emphasizing the interconnectedness of purging and healing in Ayahuasca-assisted treatment for substance dependence.
Esketamine combined with a mindfulness-based intervention for individuals with alcohol problems
This double-blind, pilot study (n=28) investigates esketamine combined with mindfulness-based intervention (MBI) for individuals with alcohol misuse problems. Esketamine enhanced psychological engagement in MBI and transiently decreased alcohol cravings, while also resulting in greater mystical experiences and dissociative states compared to placebo.
Neural mechanisms of psychedelic visual imagery
In a double-blind, placebo-controlled crossover fMRI study using dynamic causal modelling, 0.2 mg/kg psilocybin increased self-inhibition (reduced synaptic gain) in both early and higher visual areas while reducing inhibitory influence from visual-association regions onto early visual cortex, indicating enhanced top‑down feedback. These connectivity changes correlated with reports of eyes-closed visual imagery, suggesting psilocybin shifts the balance of cortical processing to amplify internally generated visual experiences.
Developing an Ethics and Policy Framework for Psychedelic Clinical Care: A Consensus Statement
This consensus statement (n=27) identifies key ethics and policy issues for integrating psychedelic therapies into clinical practice. It reports 20 points of consensus across 5 ethical issues, with relevant actors responsible for implementation, and highlights areas needing further research and deliberation.
Functional changes in sleep-related arousal after ketamine administration in individuals with treatment-resistant depression
In a randomized, double-blind crossover study of 36 people with treatment-resistant depression (TRD) and 25 healthy volunteers, ketamine altered the temporal dynamics of sleep EEG spectral power in TRD—producing earlier-night increases in delta power and later-night increases in alpha and delta. These spectral changes occurred without effects on sleep macroarchitecture (e.g. WASO, TST, REM latency), did not mediate ketamine’s antidepressant or anti‑suicidal effects, and baseline TRD showed lower total sleep time and shorter REM latency.
Effects of a Single Dose of Ayahuasca in College Students With Harmful Alcohol Use: A Single-blind, Feasibility, Proof-of-Concept Trial
In a single-blind proof-of-concept trial in 11 college students with harmful alcohol use, one dose of ayahuasca with psychological support was well tolerated and produced a short-term reduction in days drinking at 2–3 weeks that did not survive correction for multiple comparisons. The study demonstrates feasibility of the protocol and supports larger, controlled trials to assess efficacy.
The Role of Music in Psychedelic-Assisted Therapy: A Comparative Analysis of Neuroscientific Research, Indigenous Entheogenic Ritual, and Contemporary Care Models
This review evaluates the role of music in psychedelic-assisted therapies (PAT) and indigenous entheogenic ceremonies. It examines neuroscientific, psychological, and anthropological research, highlighting the need for personalized music protocols and the integration of traditional practices into modern treatment models to enhance clinical outcomes.
Adolescent Psychedelic Use and Psychotic or Manic Symptoms
In a large Swedish twin cohort, after adjusting for other substance use, lifetime naturalistic psychedelic use was associated with lower self‑reported psychotic symptoms in adolescents. However, psychedelic use interacted with genetic liability for schizophrenia or bipolar I disorder to predict higher self‑reported manic symptoms, so the observational findings warrant cautious interpretation.
Chemical cousins with contrasting behavioural profiles: MDMA users and methamphetamine users differ in social-cognitive functions and aggression
This comparative study (n=165) evaluated social cognitive functions and behaviors in chronic METH users, chronic MDMA users, and stimulant-naïve controls. METH users exhibited diminished cognitive and emotional empathy towards positive stimuli, elevated punitive social behavior regardless of provocation, and heightened trait anger. MDMA users showed a distinct rise in punitive behavior when provoked, with correlations suggesting associations between substance use patterns and social-cognitive deficits.
Single-Dose Synthetic Psilocybin With Psychotherapy for Treatment-Resistant Bipolar Type II Major Depressive Episodes
In an open‑label, non‑randomised 12‑week trial of 15 patients with treatment‑resistant bipolar II depression, a single 25 mg dose of synthetic psilocybin plus psychotherapy produced large, rapid and sustained reductions in depressive symptoms (mean MADRS change −24 points at 3 weeks; 12/15 responders, 11/15 remissions) without significant increases in mania or suicidality. These preliminary results suggest psilocybin may be an effective and safe acute treatment for bipolar II depression and merit confirmation in larger randomised controlled trials.
The Influence of Psilocybin on Subconscious and Conscious Emotional Learning
This double-blind, placebo-controlled study (n=30) investigates the learning effects of psilocybin (up to 20 mg) in a probabilistic cue-reward task with emotional cues. It finds that psilocybin preserves learning effects, is non-inferior to placebo, and suggests higher exploratory behaviour. The 20 mg group showed significantly better learning rates than placebo.